1,2-Dimethoxyethane → Tert-butyl 4-(2-(4-(ethoxycarbonyl)phenoxy)pyridin-3-YL)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 410275Notes

Reaction equation

HRID 410275 reaction equation
Br[C:2]1[C:3]([O:8][C:9]2[CH:19]=[CH:18][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.CC1(C)C(C)(C)OB([C:28]2[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH:29]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(O)C.O>[CH2:16]([O:15][C:13]([C:12]1[CH:18]=[CH:19][C:9]([O:8][C:3]2[C:2]([C:28]3[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH:29]=3)=[CH:7][CH:6]=[CH:5][N:4]=2)=[CH:10][CH:11]=1)=[O:14])[CH3:17]

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 59327082HCID 59327082, compound

Product 1

HCID 59327113Tert-butyl 4-(2-(4-(ethoxycarbonyl)phenoxy)pyridin-3-YL)-5,6-dihydropyridine-1(2H)-carboxylate

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
135 °C

Procedure

Four glass microwave reaction vessels were charged with ethyl 4-(3-bromopyridin-2-yloxy)benzoate (1.025 g, 3.18 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (1.195 g, 3.86 mmol), sodium carbonate (1.725 g, 16.28 mmol) and trans-dichlorobis(triphenyl-phosphine)palladium (II) (0.140 g, 0.199 mmol). DME (6 mL), Water (3 mL) and Ethanol (2 mL) were added and the reaction mixtures were sealed under argon and heated in a Emrys Optimizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 135° C. for 15 min. The reaction mixtures were combined and partitioned between EtOAc/water. The aqueous layer was extracted with EtOAc (3×) and the combined organic layers were evaporated onto silica gel and purified by flash chromatography (Isco (120 gram)) eluting with EtOAc:hexanes (0:1→1:4) to give a light-yellow crystalline solid. MS m/z: 425.1 [M+1].

Workup

  1. customFour glass microwave reaction vessels
  2. customthe reaction mixtures
  3. customwere sealed under argon
  4. customThe reaction mixtures
  5. custompartitioned between EtOAc/water
  6. extractionThe aqueous layer was extracted with EtOAc (3×)
  7. customthe combined organic layers were evaporated onto silica gel
  8. custompurified by flash chromatography (Isco (120 gram))
  9. washeluting with EtOAc:hexanes (0:1→1:4)
  10. customto give a light-yellow crystalline solid

Sources & evidence

ORD record
ord-a12667e2217a4b64b3425dca54061fbf
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

Loading…